Hypomethylation of the Thymosin β10 Gene Is Not Associated with Its Overexpression in Non-Small Cell Lung Cancer

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Thymosin β10 (TMSB10) is a monomeric actin sequestering protein that regulates actin cytoskeleton organization. The aberrant TMSB10 expression has been implicated in the pathogenesis of human cancers. However, its role in carcinogenesis is still controversial. To better understand the role of TMSB10 in lung tumorigenesis and its regulatory mechanism, we examined the methylation status and expression of the TMSB10 gene in non-small cell lung cancers (NSCLCs) using methylation-specific PCR (MSP) and immunohistochemistry (IHC), respectively. MSP analysis showed that the TMSB10 promoter was already unmethylated in most tumor tissues and became demethylated in 20 (14.4%) of the 139 NSCLCs. TMSB10 hypomethylation was not significantly correlated with the clinicopathological features. IHC showed that the TMSB10 protein was strongly expressed in the cytoplasm of malignant cells and its overexpression was detected in 50.0% of the tumor tissues compared to normal tissues. TMSB10 overexpression was frequently observed in sqaumous cell carcinomas compared to adenocarcinomas with border line significance (P = 0.072). However, TMSB10 methylation status was not linked to its overexpression. Collectively, these results suggest that TMSB10 hypomethylation may be a frequent event in NSCLCs, but it may not be a common mechanism underlying TMSB10 overexpression. However, further studies with large numbers of patients are needed to confirm our findings.

Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer

“…TMSB10 is upregulated in multiple human cancers and upregulation of TMSB10 contributes to cancer cell proliferation, migration and invasion via different mechanisms, and predicts poor survival [ 13 , 15 , 31 – 33 ]. However, the expression of TMSB10 has also been shown to be downregualted in ovarian cancer tissues and cells and overexpression of TMSB10 diminishes tumor growth and proliferation [ 34 , 35 ].…”

Thymosin β10 promotes tumor-associated macrophages M2 conversion and proliferation via the PI3K/Akt pathway in lung adenocarcinoma

“…TMSB10, a 43-amino acid residues β-thymosin, is found to be overexpressed in human lung cancer, liver cancer, breast cancer, ovarian cancer, gastric cancer, pancreatic cancer, thyroid cancer and renal cell carcinoma et al (17,20,(23)(24)(25)(26)(27). And TMSB10 mRNA is found to be overexpressed in TAMs of early lung adenocarcinoma compared with those in adjacent normal lung macrophages and peripheral blood monocytes (21).…”

“…TMSB10 mainly function as actin sequestering proteins to inhibit the formation of Factin. TMSB10 has been proven to be overexpressed in most human solid tumors, and regulate cancer cell proliferation and metastasis (16)(17)(18)(19)(20). Remarkably,Miriam Merad et al reported that TMSB10 mRNA was unregulated in TAMs of early lung adenocarcinoma compared with those in mononuclear macrophages of adjacent normal lung and peripheral blood (21).…”

Immunoreactivity for thymosin beta 4 and thymosin beta 10 in the adult rat oro-gastro-intestinal tract

“…On one hand, Tβ10 diminishes tumor growth, angiogenesis and proliferation 25 and Tβ10 over-expression has been related to the increase of apoptosis in human ovarian cancer cells 25 . On the other hand, Tβ10 has been associated to the progression of papillary thyroid carcinoma 26 and over-expression of the peptide has been observed in non-small cell lung cancer 27 and in pancreatic cancer. 28 The recent report by our group of a strong expression for Tβ10 in the human salivary glands during development, 29 induced us to better analyse the protein expression pattern for Tβ10 in the oro-gastro-intestinal tract in adult rats, in order to show if Tβ10 is expressed in the gastrointestinal tract in adulthood, and to compare the expression of this peptide with that reported in the human digestive tract and in annexed glands.…”